Device and method for ablative treatment of targeted areas within a body lumen

ABSTRACT

Disclosed is a cryotherapy device comprising at least one inflow channel, at least one outflow channel, control means for controlling the evacuation of expanded cryo-fluid from a body lumen, wherein the control means receive data from at least one sensor that gathers data regarding at least one parameter of the body lumen and wherein the cryotherapy device is introduced into the body lumen via an endoscope.

RELATED APPLICATION/S

This application is continuation of U.S. patent application Ser. No.15/531,466, filed May 30, 2017, which is a National Phase of PCT PatentApplication No. PCT/IL2015/051122 having International Filing Date ofNov. 22, 2015, which claims the benefit of priority under 35 USC §119(e) of U.S. Provisional Patent Application Nos. 62/104,879 filed onJan. 19, 2015, and 62/085,666 filed on Dec. 1, 2014. The contents of theabove applications are all incorporated by reference as if fully setforth herein in their entirety.

FIELD OF THE INVENTION

The invention is related to the field of ablation, includingcryoablation, cryosurgery or cryotherapy devices. Particularly,embodiments of the invention are directed to cryotherapy devices fortreating body lumen diseases.

BACKGROUND OF THE INVENTION

Cryoablation, cryosurgery or cryotherapy is a technique by whichtargeted areas, which may include undesired symptoms, lesions, or freenerve endings are destroyed or ablated by freezing. Tissue destructionby freezing includes direct injury to cells caused by ice crystalformation, as well as delayed injury that may be caused by apoptosis(regulated cells death) and/or vascular effects. Cryotherapy isperformed by utilizing a pressurized coolant (such as CO₂, LN₂, and/ornitrous oxide), in order to directly spray the cryogenic fluid onto thetreated tissue and/or to enable an indirect Joule Thompson effect tooccur (using coolants, such as, Argon, Nitrogen and/or Krypton).

Radiofrequency ablation (RFA) is used by applying monopolar or bipolarradiofrequency (RF) energy while creating a contact of an RF antenna anda targeted tissue or lesion.

The use of cryosurgery to ablate tumors is expanding, primarily due toits technical ease and low morbidity rate. A potential secondaryadvantage to the in situ freezing of malignant diseases is thecryo-immunological response, i.e., the generation of an anti-tumorimmune response triggered by the natural absorption of the malignanttissue. Clinical reports suggest that cryoablation may induce a systemicantitumor immune response, which has also been confirmed in animalmodels.

Body lumens may include bladder; uterus and others. Bladder cancer isone of the most common cancers. When a diagnosis is made at an earlystage, the majority of patients diagnosed with bladder cancer havesuperficial disease and are low grade in nature; others however, arediagnosed at a later stage, which the cancer is more invasive andaggressive so surgical intervention (including cystectomy) may beutilized. Bladder cancer has a high likelihood of recurrence; thereforetreatment and follow-up is critical in the prevention of recurrence andprogression. It is suggested to use cryotherapy or RFA methods in orderto improve treatment for bladder lesions, reduce recurrences andpotentially increase bladder preservation rate.

Additional example for bladder illness is Interstitial Cystitis (IC),also known as painful bladder syndrome, a chronic condition of bladderand/or pelvic pain, ranging from mild discomfort to severe pain.Although there is no treatment that reliably eliminates IC, medicationsand other therapies are offered to relieve pain. For example, Botoxinjections inside the bladder are thought to block the sensory nerves inthe bladder that transmit pain. It is suggested to use cryotherapy orRFA methods, ablating/harming free nerves ending, in order to improvetreatment for IC and similar conditions, in order to increase patients'comfort for longer times.

Regarding uterine illnesses and lesions, in order to avoid majorsurgical intervention, such as, hysterectomy or myomectomy,hysteroscopic procedures may be utilized. Uterine lesions may includesub-mucous fibroids or large polyps or menorrhagia with normalendometria. Additional uterine-related illnesses include thinendometrium and/or Asherman's syndrome (AS), both of which hinderconception. It is suggested to use cryotherapy methods in order toimprove treatment for uterine illnesses and lesions thus easing thetreatment and potentially increasing uterus preservation rate.Generally, cryotherapy may aid in endometrium rejuvenation and thereforeresult in an increase in the Conception success probability.

There are no known cryotherapy or RFA devices that are inserted intobody lumen through an endoscope's working channel. On the other hand,catheter devices that are inserted via an endoscope and are used fortreating the gastrointestinal (GI) tract are known in the art. The maindifferences between current GI devices to those required for body lumenstreatments are the size of the necessary insertion cavity (esophagus orcolon are significantly bigger in diameter) and the steering effort,which is minimal for current GI applications. For example, somecryotherapy devices include the use of a cryogenic fluid jet, such thatthe cryogenic fluid or coolant exits through a nozzle and is directlyapplied onto the tissue in the form of a spray. In such devices, whenthe operator manipulates the endoscope in order to direct thecryotherapy device to a specific area of interest, no major steeringeffort is required, since movement of the endoscope back and forth maybring the treated lesion to be in front of the applied spray. In some ofthe cryotherapy devices that utilize spray, an additional aspirationchannel is needed in order to evacuate the spray's expanded fluids thuspreventing unwanted lumen inflation or tissue perforation. Such anaspiration channel requires additional space, either within the workingchannel or outside of the endoscope. In addition the distance of thenozzle from the targeted area is not constant when the cryotherapycatheter is not fixed to the endoscope. As a result, the treatmentoutcome is not predictable and it may be difficult for the physician tofollow the cryosurgery protocol.

There are no known RFA devices that are inserted into body lumen whilebeing applied through endoscope's working channel for bladder or uterustreatments or for any other body lumen treatments. However, there arecatheter RFA devices that are manipulated via an endoscope and are usedfor treating the gastrointestinal (GI) tract. Those RFA devices arewider in size than the endoscope so there is a need to insert the deviceinto the working channel from the distal side of the endoscope resultingin an overall inserted device that is wider than the endoscope. Inaddition, in order to remove the device one needs to remove theendoscope as well.

There is no known use for cryotherapy devices in combination with immunemodulation therapy within a body lumen, either using an endoscope ornot.

Therefore, there is a need for a modified endoscopic ablation device(cryotherapy, REA) that allows ablating tissue within body lumens,wherein the device has the ability to perform sharp angular movements,enabling easy manipulation of the device towards a targeted area withrespect to the endoscope through which it passes. There is also a needfor a modified cryotherapy device with ability to evacuate coolantexpanded fluids through the limited size of the body lumen entrance.There is also a need to improve cryo-immunological methods and to adaptthem to cryoablation within a body lumen.

SUMMARY OF THE INVENTION

Embodiments of the invention are directed to a cryotherapy devicecomprising:

-   at least one inflow channel;-   at least one outflow channel;-   control means for controlling the evacuation of expanded cryo-fluid    from a body lumen;-   wherein the control means receive data from at least one sensor that    gathers data regarding at least one parameter of the body lumen and    wherein the cryotherapy device is introduced into the body lumen via    an endoscope.

According to some embodiments, the inflow channel and the outflowchannel are the same channel. According to some embodiments, the overalldiameter of the inflow channel, the outflow channel and any otherchannels or devices introduced is between 0.8-9.0 mm. According to someembodiments, wherein at least one tube or catheter is fed through atleast one channel, and wherein the tube or catheter is at leastpartially flexible, bendable, kink resistant or any combination thereof.

According to some embodiments, at least one inflow channel and at leastone outflow channel are part of a multi-channel fabricated or extrudedtube or catheter. According to some embodiments, the inflow channel, theoutflow channel, or both, are at least partially braided, coiled, orboth. According to some embodiments, the inflow channel is attached toat least one inflow nozzle, and wherein the inner diameter of any one ofthe inflow nozzles is in the range of 0.05-0.3 mm. According to someembodiments, the outflow channel is attached to at least one outflowopening, and wherein the inner diameter of any one of the outflowopenings is in the range of 0.5-4.0 mm.

Further embodiments of the invention are directed to a method oftreating tissue within a body lumen, the method comprising:

-   introducing a cryotherapy device into a body lumen via an endoscope;-   injecting cryo-fluid through at least one inflow channel of the    cryotherapy device, directly or indirectly, into the body lumen,    such that the cryo-fluid expands, directly or indirectly, in the    body lumen thereby freezing at least part of the treated tissue; and-   evacuating expanded cryo-fluid, directly or indirectly, through at    least one outflow channel of the cryotherapy device, from the body    lumen;-   wherein the evacuation of the cryo-fluid is controlled by control    means receiving data from at least one sensor that gathers data    regarding at least one parameter of the body lumen.

According to some embodiments, at least one inflow channel and at leastone outflow channel are the same channel, wherein the direction of flowtherethrough is controlled by the control means. According to someembodiments, at least one inflow channel and at least one outflowchannel are part of a multi-channel fabricated or extruded tube orcatheter. According to some embodiments, sharp angular movements of theendoscope do not kink the inflow channel or the outflow channel.According to some embodiments, the inflow channel and the outflowchannel are at least partially bendable, flexible or kink-resistant.According to some embodiments, the inflow channel, the outflow channel,or both, are at least partially braided, coiled, or both.

According to some embodiments, the body lumen is a bladder, a cervix, aprostate or a uterus. According to some embodiments, body fluids areevacuated from the body lumen through at least one outflow channel.According to some embodiments, the control means receives parametersregarding the internal pressure in the treated body lumen, thetemperature of the treated body lumen, flow rate, flow time, or anycombination thereof. According to some embodiments, the cryo-fluid isindirectly injected into the body lumen, wherein it is injected into afolded component. According to some embodiments, the folded component isa cryo-balloon. According to some embodiments, the cryo-fluid isinjected into a catheter, wherein the catheter is inserted into the bodylumen though does not have an opening into the body lumen, and whereinthe expanded cryo-fluid is evacuated from within the catheter.

According to some embodiments, the cryo-fluid is injected together withat least one additional active component. According to some embodiments,the active component is a biological, immunological, chemical,nanoparticle or a chemotherapy entity. According to some embodiments,the active component is selected from mitomycin C, doxorubicin anddendritic cells. According to some embodiments, the cryo-fluid isselected from liquid nitrogen, carbon dioxide (CO₂), nitrous oxide(N₂O), or any combination thereof.

Further embodiments are directed to a cryotherapy device, which ispassed through an endoscope, for treating at least one targeted regionwithin a body lumen, the device comprising:

-   -   a folded ablating cryo-balloon;    -   means for introducing the folded cryo-balloon into a body lumen        though an endoscope; and    -   means to unfold the cryo-balloon inside the body lumen.

According to some embodiments, the cryo balloon has regions that havedifferent degrees of compliance, and wherein a region of thecryo-balloon that is active in transferring cold temperature to thetargeted regions, is brought into contact with a targeted region byinflation of the balloon, movements of the balloon, or both inflationand movements of the balloon. According to some embodiments, thecryo-balloon is compliant, semi-compliant, non-compliant, or anycombination thereof. According to some embodiments, the diameter oraverage diameter of the cryo-balloon, when folded is below 2.5 mm.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other objects and advantages of the invention will beapparent upon consideration of the following detailed description, takenin conjunction with the accompanying drawings, in which the referencecharacters refer to like parts throughout and in which:

FIGS. 1A to 1D illustrate schematic lengthwise sectional views of acryotherapy device, during cryotherapy procedure, introduced into thetreated lumen via an endoscope in accordance with some embodiments ofthe present invention;

FIGS. 2A, 2B and 2C illustrate schematic lengthwise sectional views of acryotherapy system, specifically presenting means by which fluids maypass in and out of the treated area in accordance with some embodimentsof the present invention;

FIG. 3 illustrate a schematic lengthwise sectional view of a cryotherapysystem and specifically the means by which the device's distal end ispositioned and fixed in accordance with some embodiments of the presentinvention;

FIGS. 4A to 4E illustrate schematic lengthwise sectional views of acryotherapy device's distal end in accordance with some embodiments ofthe present invention;

FIGS. 4F to 4H illustrate schematic transverse cross-sectional views ofa cryotherapy device's distal end, in accordance with some embodimentsof the present invention;

FIGS. 5A to 5D illustrate schematic lengthwise sectional views of acryotherapy device introduced through an endoscope, during a sharpangulation scenario, in accordance with some embodiments of the presentinvention;

FIGS. 6A to 6E illustrate schematic lengthwise sectional views of thedistal end of a cryotherapy device, which includes specific nozzles,providing different types of sprays, in accordance with some embodimentsof the present invention;

FIGS. 7A and 7B illustrate schematic lengthwise sectional views of acryotherapy device introduced via a rigid endoscope and especially theuse of endoscope's in-flow and out-flow channels, in accordance withsome embodiments of the present invention;

FIGS. 8A and 8B illustrate schematic lengthwise sectional views of acryotherapy device introduced via an endoscope within the treated lumenduring ablation procedure in accordance with some embodiments of thepresent invention;

FIGS. 8C and 8D illustrate schematic lengthwise sectional views of acryotherapy inflated device introduced via an endoscope within thetreated lumen during an ablation procedure in accordance with someembodiments of the present invention;

FIGS. 8E to 8G illustrate schematic lengthwise sectional views of acryotherapy inflated device introduced inside lumen during an ablationprocedure in accordance with some embodiments of the present invention;and

FIGS. 9A and 9B illustrate schematic lengthwise sectional views of thedistal end of a cryotherapy device, specifically presentingcryo-balloons, in accordance with some embodiments of the presentinvention.

It will be appreciated that for simplicity and clarity of illustration,elements shown in the figures have not necessarily been drawn to scale.For example, the dimensions of some of the elements may be exaggeratedrelative to other elements for clarity. Further, where consideredappropriate, reference numerals may be repeated among the figures toindicate corresponding or analogous elements.

DETAILED DESCRIPTION

In the following detailed description, numerous specific details are setforth in order to provide a thorough understanding of the invention.However, it will be understood by those skilled in the art that thepresent invention may be practiced without these specific details. Inother instances, well-known methods, procedures, and components have notbeen described in detail so as not to obscure the present invention.

Embodiments of the invention are directed to devices and systems forcryotherapy, which may be introduced into a body lumen through anendoscope or any other appropriate means (e.g., inserting a catheterdirectly into the lumen with no visualization or with outer imagingmeans, such as an ultrasound, CT and the like). The present invention isfurther directed to cryotherapy methods within body lumen. According tosome embodiments, the cryotherapy methods include cryo-immunologicalprocesses.

It is noted that the term “endoscope” as used herein, is intended toinclude any type of known endoscope, as well as any type of sheath,catheter, tube or the like, that may be inserted into the body andthrough which any necessary working channels, optic devices and the likemay be placed in the body lumen. Accordingly, the endoscope may includeinherent optical means or otherwise, the optical means may be insertedthrough any type of sheath and the like, such that the optical means maybe changed during the procedure, i.e., several different kinds of opticsmeans may be used throughout the procedure. Any other sensors may alsobe inherent in the endoscope or may be inserted therethrough into thebody lumen. It is noted that the term “working channel”, or any otherequivalent term used herein, may be an integral path through anendoscope or a path available through any means, such as a sheath,catheter, tube or the like, through which any devices and/or sensors,such as optics, may be inserted into the body lumen.

According to some embodiments, the cryotherapy device includes two ormore, channels, tubes, catheters, or the like, which allow both theinjection of pressurized fluids and the evacuation of expanded fluids,wherein a pressurized fluid is injected into the lumen via at least onechannel and the expended fluid is evacuated from the lumen through atleast one second channel. It is noted that catheters, tubes and the likeare interchangeably used herein, unless specifically mentionedotherwise. According to some embodiments, at least one injection channeland at least one evacuation channel are inserted into the body lumen viaan endoscope. According to some embodiments, any channel may pass or befed through any one of the other channels. According to otherembodiments, the same channel may be used for both injection andevacuation, using any appropriate type of sensor and/or dedicatedalgorithm to control flow direction, relative amounts and timing. It isnoted that although pressurized and expanded fluids are related toabove, any type of fluid may be introduced/released from the systemaccording to any one of the above embodiments. It is noted that, asknown in the art, the term “fluid” includes both gas and liquid.

Embodiments of the invention further include cryotherapy devicescomprising at least one evacuation means as well as control means, bywhich the evacuation of the expanded fluid, and possibly the injectionof the pressurized fluid, are controlled. The control means may beautomatic, predefined, electronic, manual, and the like. The cryotherapydevice may further include any number or type of sensors, wherein thecontrol means receives data from those sensors and controls theevacuation and/or the injection according to predefined values,according to manual decision, according to values that may change duringthe process etc. Without such control means it is possible that pressurewould accumulate in the targeted organ, possibly even causing rupture,since the evacuation may not be sufficient. Further, the treated bodylumen may have body liquid in it (e.g., urine in the bladder). That bodyliquid may freeze due to the cryotherapy process, possibly hindering theevacuation of the expended cryo fluid and therefore, it is important toinclude sensors in the system according to which the control meanscontrol the evacuation and possibly the injection, such that the treatedlumen is not harmed. According to some embodiments, any number ofsensors is inserted into the body lumen. According to some embodiments,any number of external sensors, such as ultra-sound, X-ray and the likemay be used together with, or possibly instead of, internal sensors.

According to some embodiments, the inflow may be stopped when thepressure in the lumen is above between about 30 mBar and 10 mBar.According to some embodiments, the outflow evacuation may be continueduntil the pressure in the lumen is below between about 20 mBar to 10mBar. According to some embodiments, the inflow may be stopped when thetemperature in the lumen is below about 5-10 deg C. According to someembodiments, the inflow may be initiated when the temperature in thelumen is above about 15-20 deg C. According to some embodiments, bothtemperature and pressure, as well as any other appropriate parametersmay be used for controlling the system.

Therefore, lumen, such as uterus, pelvis, bladder, kidneys, urethra, andureters can be treated according to this invention, even though gassescannot be naturally evacuated therefrom. According to some embodiments,the dynamics of the system, which include both injection of cryo-fluidas well as the evacuation thereof, while monitoring and controlling boththe injection and the evacuation during the entire process, preventsliquids or vapors within the lumen from freezing, thus preventingblockage and the like. The combination of the injection, evacuation andcontrol provide the necessary dynamics for the system to operateproperly. Further, even lumen having small diameter entrances, such asureters, may be treated, since the diameter of the injection andevacuation tubes may be relatively small (about 0.8-4 mm overalldiameter of all of the tubes together or about 4.0-9.0 mm overalldiameter of all of the tubes, particularly if including optics and thelike), and further, one tube, or two adjacent tubes, may be used inorder to further limit the diameter, since each additional tube usedraises the overall diameter. It is noted that small diameters, e.g.,about 0.8-9.0 mm overall diameter, may include not only the injectionand evacuation channels, but also any other channels, devices, sensorsand the like, e.g., optic devices, that are introduced into the bodylumen. According to some embodiments, the overall diameter of the inflowand outflow channels is between about 0.8-4.0 mm. The diameter of theouter sheath may be between about 5.0-9.0 mm, and the outer diameter ofthe optic device is between about 3.0-5.0 mm.

According to some embodiments, bladder, cervix, prostate, urethra,ureter or uterus conditions are treated. According to furtherembodiments, cancers of the bladder, cervix, prostate, urethra, ureteror uterus are treated. Benign growths may be treated as well. Painconditions in the bladder, cervix, prostate or uterus may also betreated. According to further embodiments, any type of urinary tractconditions may be treated, including upper tract cancer, interstitialcystitis, bladder pain syndrome, overactive bladder (OAB) and the like.

The distal end of the cryotherapy device may include any number ofholes, nozzles, fissures and the like, through which fluids may beinjected/introduced/released into the body lumen. According to someembodiments, the fluids may be injected into the lumen together with anyadditional material, such as chemotherapy, immunotherapy and/or otherchemical or biological agents. The additional material may be introducedat the same time, prior to and/or after the cryotherapy treatment foroptimal results. The introduced fluid is related to herein also as a“coolant” a “cryo-fluid” and the like. It is noted that the coolant isable to ablate/freeze any desired treated region. According to someembodiments, the distal end of the cryotherapy device includes a nozzledesigned for directly spraying fluid onto the targeted area and/or itssurroundings. The distal end of the cryotherapy device may furtherinclude evacuation means in order to evacuate expanded fluid from a bodylumen. According to some embodiments, the cryo-fluid is selected fromliquid nitrogen, carbon dioxide (CO₂), nitrous oxide (N₂O), or anycombination thereof. According to some embodiments, the cryo-fluid isselected from argon, nitrogen, krypton or any combination thereof, whichmay additionally be relevant when the cryo-fluid does not directlycontact the body tissue. According to other embodiments, it may furtherinclude any additional material, such as chemotherapy, immunotherapyand/or other therapeutics such as chemical or biological agents.According to some embodiments, the additional material is introducedinto the body lumen prior to, during and/or after the cryo treatment.

It is noted that the terms “targeted region”, “targeted area”, “treatedregion”, “treated area”, “treated lumen”, “targeted lumen” and the likeare interchangeable and are intended to include any type of conditionthat may be treated cryogenically, such as lesions (including cancerousand benign tumors, cysts, polyps and the like), nerves/nerve endings,and various symptoms, even when their specific origin is not fullyunderstood.

According to other embodiments, the coolant remains within the injectionchannel (e.g., a catheter, tube and the like) and expands therein, sothat the cold temperature is transferred into the tissue by a mediatingdistal section of the cryotherapy device. According to such embodiments,since the coolant remains in the injection channel, there is no need toevacuate the coolant from the body lumen.

According to some embodiments, the mediating distal section of thecryotherapy device is a cryo-balloon, wherein the cryo-balloon isintroduced into the treated lumen via an endoscope. The cryo-balloon maybe non-compliant, such that it withstands high pressures. If the balloonis non-compliant, the size of the balloon is chosen according to thesize of the lumen into which it is inserted or according to shape of atreated area. According to other embodiments, the balloon may besemi-compliant or compliant. According to further embodiments, differentsections of the cryo-balloon may have different degrees of compliance.The different parameters of the balloon, including the compliance of thevarious sections thereof, the shape of the cryo-balloon, the size of thecryo-balloon, etc., may change according to the treated lumen, thetargeted area in the lumen, and the like. The balloon may be circular,oval, tubular, or have any flat, or partially flat surfaces. The balloonmay also be wide in certain areas and narrow in others, depending on theintended use. When inflated, or partially inflated, the balloon maylocally contact only the treated area, not the entire lumen in which theballoon is used. According to other embodiments, the inflation of thecryo-balloon, e.g., in the urethra or ureters, may bring the balloon, orparts thereof, into contact with the entire circumference of the treatedarea. According to some embodiments, external force, e.g., movements bythe user of the device, possibly together with inflation, bring, atleast part of the cryo-balloon, into contact with the treated area.

According to some embodiments, the diameter or average diameter of thecryo-balloon, when folded (when inserted through an endoscope or aworking channel) is below 2.5 mm. According to some embodiments, thediameter or average diameter of the cryo-balloon, when folded (wheninserted through an endoscope or a working channel) is below 2.0 mm.According to some embodiments, the diameter or average diameter of theballoon, when folded (when inserted through an endoscope or a workingchannel) is below 1.5 mm.

Further, the balloon may be contacted with the targeted area by balloonexpansion, partial balloon expansion, and/or by movements of the balloonthat may be controlled externally by the user and/or by any appropriatemechanical and/or electronic means. The balloon expansion and/ormovements may further be controlled according to data received from anyinternal or external sensors.

It is noted that the injection and evacuation channels are related toherein also as catheters, tubes and the like.

According to some embodiments, the cryotherapy device may include aflexible or a kink resistant catheter, such as braided or coiled tube,which may allow sharp angular movement, thus enabling targeted areas tobe targeted easily regardless of their position within the body.

According to some embodiments, the cryotherapy device includes a singlenozzle at the distal end of the device, allowing the operator to performthe treatment within the endoscope's field of view. According to otherembodiments, the device includes at least two nozzles, wherein any twonozzles may be positioned in the same or different directions, relativeto one another. For instance, any one of the nozzles may be pointeddownward, in the distal direction, while other nozzles may be pointedsideways, at any desired angle and distance from the distal end of thedevice, thereby allowing a multi directional treatment that may treatdifferent parts of the same targeted region, several targeted areas atonce, etc. According to some embodiments, one or more of the nozzles hasan opened and closed configuration. Further, any one of the nozzles maybe partially opened or closed for any time period required. According tosome embodiments, any number of nozzles may be electronicallycontrolled, such that the practitioner using the device may use anynumber of the existing nozzles at any time point, according to thedesired treatment. According to some embodiments, the user pre-definesthe specific nozzles to be used. According to other embodiments, duringthe procedure, any one of the nozzles may be opened, partially opened,or closed at any time point, as desired, by any appropriate means,including designated sensors, computerized applications, user commandsand the like.

According to some embodiments, a folded component, such as acryo-balloon may be attached to any part of the distal end of thecryotherapy device. Accordingly, injected cryo-fluid, possibly togetherwith any other appropriate pressure source, inflates the balloon, whichin turn freezes at least part of the treated tissue. According to someembodiment, prior to the injection of cryo-fluid, the balloon isinflated by any other appropriate pressure source, allowing thepreparation of the balloon for cryo-treatment, checking or testing thesystem or certain parameters thereof, and the like. The inflation of theballoon, including inflation rate, size etc. may be controlled by anynumber of sensors, as detailed above regarding the injection throughnozzles. Further, any one of the nozzles may be attached on the outsideof the nozzle to a cryo-balloon, so that when the cryo-fluid exits thenozzle it inflates the balloon that is attached to the outside of thenozzle.

Thus, according to some embodiments, the cryo-fluid is injected directlyinto the body lumen, i.e., it comes in direct contact with at least partof the tissue of the body lumen. According to such embodiments, thecryo-fluid is injected directly into the body lumen through any numberof nozzles, holes, fissures and/or valves, as detailed herein. Further,if the cryo-fluid is directly injected into the body lumen, it is alsodirectly evacuated therefrom, by any means detailed herein. According toother embodiments, cryo-fluid may be indirectly introduced into the bodylumen, such that it does not come in direct contact with the tissue ofthe body lumen; rather, it is injected into any appropriate componentthat is positioned inside the body lumen, e.g., a catheter, acryo-balloon, a tube or the like, which does not include an opening intothe body lumen. The cryo-fluid expands within that component, therebycooling at least part of the treated tissue. The cryo-fluid may then beindirectly evacuated from the body lumen, i.e., it is evacuated from thecomponent into which it was injected, The cryo-fluid may be evacuated byactive or passive means.

According to some embodiments, the folded component is a cryo-balloonwhich is being inflated and/or filled with coolant within the lumen inorder to treat the desired area.

According to other embodiments of the current invention, any one of theendoscope's existing ‘in-flow’ and ‘out-flow’ channels may be used inorder to introduce materials into or evacuate materials from the bodylumen (e.g. evacuating cryotherapy expanded fluids).

According to some embodiments, the cryotherapy procedure is performed hicombination with any other type of treatment, including intraluminalchemotherapeutic therapy and/or immunotherapy agents. It is noted thatthe cryo-fluid may be injected together with any other activecomponents. As noted above, the additional active components may beintroduced at the same time, prior to, and/or after the cryo-treatment.

The tissue cells that were frozen by the cryo-treatment are removed fromthe body, inter glia, through the lymph system, wherein an immunologicalresponse may be triggered, which may act against such cells in any partof the body, not only the part treated by cryo-therapy. According tosome embodiments, the introduction of additional active components intothe body lumen before or during the cryo-treatment, may cause thetreated tissue to react differently to the cryo-treatment, and further,when introduced into the lymph system, the cells together with theadditional active ingredient, may cause an enhanced immune response.

The additional active ingredient may be any immunological, chemical,chemotherapeutic, biological or nanoparticle entity, including, thoughnot limited to mitomycin C, doxorubicin, dendritic cells, and the like.

Reference is now made to FIGS. 1A to 1D, which illustrate schematiclengthwise sectional views of embodiments of a cryotherapy device 10during cryotherapy procedure that is fed into the treated lumen 11through endoscope 16. As shown in FIG. 1A, jet 13, which may comprise anexpanded high pressure cryogenic fluid, is sprayed from distal end 14 ofdevice 10 and is directed at treated region 12, which may be a benign orcancerous tumor, a cyst, a polyp a free nerve ending, or a region inwhich certain symptoms (pain and the like) occur, even if their specificorigin is not known, causing the treated region 12 to be frozen, andthereby, treated or ablated.

As presented in FIG. 1B, body lumen 11 may include more than onetargeted region, e.g., regions 12 a, 12 b and 12 c. Accordingly, thedistal end 14 of device 10, may include more than one nozzle (notshown), wherein the jets 13 a, 13 b and 13 c originating from eachnozzle are directed at each one of the targeted region. According tosome embodiment, the distal end 14 includes numerous nozzles, each ofwhich may have an opened and closed configuration. The nozzles may beutilized, i.e., opened, according to their relative position to thetargeted region, such that the nozzles pointing at targeted region areopened and therefore, cryogenic fluid exiting those nozzles is sprayeddirectly at the targeted regions.

As presented in FIG. 1C, device 10 includes both inflow 133, whichprovides jet 13 (or any number of jets, as presented in FIG. 1B), andoutflow 177, for evacuating, e.g. expanded fluid 17 from lumen 11. Theenlarged, portion of device 10 shows that the tube for inflow 133 may bepositioned within the tube for outflow 177; however, according todifferent embodiments, they may be positioned in any relation to oneanother. In addition, there may be any number of outflow and inflowtubes.

According to some embodiments, and as illustrated in FIG. 1D, endoscope.16 may be used also at sharp angles, in order for jet 13 to reachtreated region 12, no matter where treated region 12 is positioned inbody lumen 11

Reference is now made to FIGS. 2A, 2B and 2C, which illustrate schematiclengthwise sectional views of a cryotherapy system, specificallypresenting the means by which fluids flow in and out of the treated areain accordance with some embodiments of the present invention. Accordingto some embodiments, cryotherapy system 20 includes a source ofpressurized coolant 201 and evacuation means 202. Evacuation means 202may be dedicated to cryotherapy system 20, general evacuation means, anoutlet to the surrounding atmosphere, or any other appropriate means bywhich material, e.g., expanded fluids, may be evacuated from the system.According to some embodiments, evacuation means 202 includes suctionprovided by any appropriate pump, vacuum, or the like. According to someembodiments, evacuation means 202 may be attached to the proximal end ofcryotherapy device 10. According to some embodiments, the evacuationmeans 202 are attached to cryotherapy device 10 via junction 28.

According to some embodiments, and as illustrated in FIG. 2A and 2B, acryotherapy catheter 224 is inserted into the endoscope 16 such that itsdistal end 24 reaches the endoscope's distal end while the proximal endof cryotherapy catheter 25 remains outside of the proximal end ofendoscope 16. According to some embodiments, proximal end 25 isconnected to junction 28 as detailed herein. According to someembodiments of the current invention simultaneous inflow 133 and outflow177 are allowed (FIG. 2B). Seal 28 a may prevent potential mixturebetween the two flows. This may be necessary when the two flows areoriented in a coaxial manner inside the endoscope, such that there is aneed to separate the flows outside the endoscope. Optional suction trap203 may collect evacuated fluids and may protect evacuation means 202from being contaminated.

According to some embodiments, and as illustrated in FIG. 2C, junction28 includes valve 28 b, which controls inflow 133 and outflow 177, suchthat they do not flow simultaneously; rather, valve 28 b determineswhether inflow 133 is activated or whether outflow 177 is activated.Valve 28 b may be operated according to any appropriate means, includingpredefined settings, electronic means, manual operation, and the like.Control of valve 28 b may take pressure, time, targeted region reactionand the like into account.

According to some embodiments, the inflow may be stopped when thepressure in the lumen is above between about 30 mBar and 100 mBar.According to some embodiments, the outflow evacuation may be continueduntil the pressure in the lumen is below between about 20 mBar to 10mBar. According to some embodiments, the inflow may be stopped when thetemperature in the lumen is below about 5-10 deg C. According to someembodiments, the inflow may be initiated when the temperature in thelumen is above about 15-20 deg C. According to some embodiments, bothtemperature and pressure, as well as any other appropriate parameters,may be used for controlling the system.

According to some embodiments cryotherapy system may include a controlmechanism, which controls coolant injection and/or expanded fluidevacuation. The control mechanism may include predetermined parameters(e.g. cyclic) and/or may include parameters defined with feedback todata collected from the system by any appropriate sensors, such asdistal pressure, distal temperature, proximal pressure, proximaltemperature, comparing flow entered to flow evacuated, operation timeand other optional measured parameters. When such feedback relatedcontrol is implemented, relevant sensing and control means are to bepart of the embodiment (like CPU, firmware, flow sensor, pressuresensor, clock, etc.)

Reference is now made to FIG. 3, which illustrates schematic lengthwisesectional views of an embodiment of the cryotherapy system, specificallythe location and possible fixing of the device's distal end. Accordingto some embodiments a cryotherapy system 20 includes a source ofpressurized coolant 201 and evacuation means 202, which are mutuallyconnected to proximal end 35 of cryotherapy device 10 at junction 28.Optional suction trap 203 may collect evacuated fluids as required.

According to some embodiments, in order to define the distance betweenthe catheter's distal end 24 from the distal end of endoscope 16, afixation mechanism is implemented. The fixation means may be attached toproximal end 35 of cryotherapy device 10. Notches 35 a provide aspecific distance between catheter's distal end 24 from the distal endof endoscope 16 and limiter 35 b may be moved and/or fixated accordingto each specific notch or scale in relation to operator's definition ofdesired distance. The desired distance may be predefined, controlled byany appropriate electronic means, controlled manually, or the like. Thedesired distance may be changed during the operation of the device ormay be constant throughout the cryotherapy. Limiter 35 b may be fixed ina certain notch 35 a by any appropriate securing means, such as clips,screws, elastic bands and the like.

Reference is now made to FIGS. 4A to 4D, which illustrate schematiclengthwise sectional views of a cryotherapy device's distal end inaccordance with some embodiments of the present invention. It is notedthat any number of tubes/catheters may be used both for inflow andoutflow in and from the system, respectively. It is further noted thatany appropriate configuration of those tubes/catheters in relation toone another is possible, including one inside the other, two adjacenttubes and the like. Some embodiments include a tube/catheter comprisingseveral paths through which fluid may flow in any defined direction.According to some embodiments, distal end 24, comprises paths for thesimultaneous flow of pressurized coolant inflow 133, to be sprayedthrough nozzle 49, and evacuated expanded fluid outflow 177.

According to some embodiments, as presented in FIG. 4A, distal end 24has inflow nozzle 49 and outflow openings 407 in a close or similarplane.

According to other embodiments, as illustrated in FIG. 4B, inflow nozzle49 and outflow openings 407 are positioned in different planes of distalend 24. When in different planes it is possible that the inflow andoutflow do not interfere with one another, thereby optimizing thefreezing efficacy of inflow 133 as well as the evacuation of outflow177.

According to other embodiments, as illustrated in FIG. 4C, outflowopenings 407 are positioned at a changing distance from inflow nozzle49, e.g., having an inclined cross-section. This may also provideinflows and outflows that do not interfere with one another. By having achanging distance between inflow nozzle 49 and outflow openings 407, theevacuated fluid passing through outflow openings 407 should notinterfere with inflow 133, though is still, at least partially, in closeproximity to nozzle 49, such the efficient evacuation/suction of outflow177 through outflow openings is possible.

According to other embodiments, as illustrated in FIG. 4D, distal end 24includes several side outflow openings 407. The side Outflow openings407 may be circumferential or partially circumferential. Utilizing suchside openings distances outflow 177 and inflow 133 from one another,such that they do not interfere with one another. Further, since thereare several outflow openings 407 they can evacuate fluid efficiently,even though they are positioned on the sides of distal end 24.

Reference is now made to FIG. 4E, which illustrates schematic lengthwisesectional view of a cryotherapy device's distal end 24 in accordancewith another embodiment of the present invention. According to someembodiments, distal end 24 does not comprise any openings into thetreated lumen, such that the coolant remains and expands within distalend 24. According to such an embodiment, the transfer of coldtemperatures into the tissue is mediated by mediating region 44 ofdistal end 24. Thus, pressure does not build up in the treated bodylumen. According to some embodiments, in order to further optimizetemperature drop, i.e., freezing of the treated area, feedback coil 409may be used for pre-cooling pressurized coolant inflow 133 with thealready cooled-expanded fluid of outflow 177.

According to some embodiments, mediating region 44 is prepared from hardmaterial such as stainless steel, copper or brass. According to otherembodiments, the mediating region 44 may be at least partially preparedfrom an expandable or inflatable material, such as a balloon, therebyenabling distal end 24 to assume the geometry of the treated lumen,thereby optimizing the treatment. According to further embodiments, theinflatable/expandable part of mediating region 44 may beinflated/expanded such that it assumes a shape that does not necessarilyfill the treated lumen, though is able to touch or surround the targetedregion. According to some embodiments, the inflatable/expandable part ofmediating region 44 may be inflated/expanded according to predefinedparameters, according to signals received from any appropriate sensors,automatically or manually. Further, the rate and size ofinflation/expansion may differ throughout the cryotherapy treatment. Asdetailed above, the mediating region may be prepared from a compliant(15-200%, e.g., prepared from polyurethane, nylon elastomers and otherthermoplastic elastomers), non-compliant (0-8%, e.g., prepared from PET,nylon and others) or a semi-compliant material (5-15%, e.g., preparedfrom polyamides and engineered nylons as polyether block amide (Pebax®),and PET and polyurethane), that may be of any appropriate size and shapeand that further may be brought into contact with the treated region byexpansion and/or by moving the mediating region, possibly, externally bythe user. The expansion and/or the movement may be controlled by anyappropriate means and may further be controlled according to datagathered by any internal or external sensors.

Reference is now made to FIGS. 4F to 4H, which illustrate schematictransverse cross-sectional views of a cryotherapy device. According tosome embodiments, inflow 133 flows through tube/catheter 33 that ispositioned within tube/catheter 77, through which outflow 177 flows.According to some embodiments, tubes/catheters 33 and 77 may be separatefrom one another, positioned as desired during or before the cryotherapytreatment. According to other embodiments, tubes/catheters 33 and 77 areintegrated together, such that essentially only one such tube/catheterexists, including passageways for both outflow 177 and inflow 133. Thus,two tubes may be used to fabricate the desired shape or otherwise, atube may be extruded to have the appropriate channels. It is noted thatalthough the embodiment presented in FIG. 4F shows tube 33 within tube77, according to other embodiments, tube 77 may be placed within orbeside tube 33. This is true for the embodiments shown in FIGS. 4G and4H as well, wherein the position of any of the tubes may be changedaccording to the system/user requirements. Further, according to someembodiments, the outer tube, in the figure tube 77, may be theendoscope's working channels, through which tube 33 (or vice versa)passes.

According to further embodiments, as presented in FIGS. 4G and 4H, thetransverse cross section of distal end 24 has several openings, whereinoutflow 177 passes through some of the openings, while inflow 133 passesthrough other openings. Any one of the openings may serve as an inflow,outflow or a sensing passage, according to the system/user requirements.A sensing passage is one through which at least one sensor passes,wherein data gathered from that sensor may be used to control the systemand the use thereof. Further, any one of the passages may serve foreither outflow or inflow at different times during the cryotherapytreatment, according to predefined conditions, parameters definedaccording to data received from any appropriate sensors, electronicallyor manually. It is noted that although FIGS. 4A-4H present specificembodiments of the distal end of the device, any other embodimentsincluding any number or position of inflow/outflow tubes may beimplemented. It is also noted that any such tubes may be prepared from acombination of several tubes, fabrication and/or extrusion.

According to other embodiments, any number of the paths/tubes/catheterspassing through endoscope 16 may be used for the sensing means that maybe needed for controlling the body lumen pressure or temperature, suchas pressure sensing and/or temperature sensing or for any other sensorsrequired. Additional sensing means may include sensors for calculatingthe lumen's volume (e.g. initial volume and changes in volume due to inand out flows), sensors for sensing the lumen's wall thickness (e.g. byultrasound or laser light) and the like.

Reference is now made to FIGS. 5A to 5D, which illustrate schematiclengthwise sectional views of a cryotherapy device that is fed into thebody lumen via an endoscope during sharp angulation scenario, inaccordance with some embodiments of the present invention. According tosome embodiments, cryotherapy device 10, which is illustrated in FIG.5A, is inserted into the working channel of endoscope 16 such thatdistal end 24 of cryotherapy device 10 reaches the distal end ofendoscope 16. When the angulation of endoscope 16, including sharpangulation, is necessary for passing through certain passages and/or fortargeting the treated region, it is necessary that no kinks are formedin cryotherapy device 10. Such kinks, for example, kinks 505 a, as shownin FIG. 5A, may interfere with the inflow and outflow of fluids throughcryotherapy device 10. Accordingly, cryotherapy device 10 may include atube/catheter that is flexible, bendable and/or kink resistant, such asbraided tube 505 b (FIG. 5B) or coiled tube 505 c (FIG. 5C), to assistwith angulation, including sharp angulation, allowing the targeting ofany treated regions throughout the treated lumen, as well as passingthrough any necessary passageways in order to reach the body lumen.According to some embodiments, cryotherapy device 10 includes atube/catheter, wherein only certain sections of the tube/catheter areflexible, bendable and/or kink resistant. According to otherembodiments, cryotherapy device 10 includes a tube/catheter that isflexible, bendable and/or kink resistant in its entire length.

According to some embodiments, the cryotherapy device may includenon-rigid flexible semi-inflatable catheter 54 a (FIG. 5D) which may beinflated by one of device's flows (pressurized or expanded fluid) up tothe working channel geometry. This is especially important when theworking channel undergoes angulations. According to some embodiments, amore rigid component 54 b may be found around the distal end of thecatheter (FIG. 5D), such that the rigid components aids in maintainingthe orifice shape and direction of the catheter even when expanded, inorder to keep the desired sprayed flow 53.

Reference is now made to FIGS. 6A to 6E, which illustrate schematiclengthwise sectional views of a cryotherapy device's distal end,specifically presenting embodiments of nozzles/holes/valves in theinflow tube/catheter and related inflow sprays of cryo-fluid inaccordance with some embodiments of the present invention. A cryotherapydevice, according to embodiments of the present invention, may comprisea pressurized coolant tube/catheter through which cryogenic fluid maypass until it exits the tube/catheter through a nozzle/hole/valve, thusentering the treated body lumen. Such nozzles/holes valves may bedesigned in any appropriate manner, such that the stream of cryogenicfluid exits into the body lumen, possibly directed at the treatedregion. According to one embodiment, as presented in FIG. 6A, inflow 133exits tube 60 via hole (nozzle/orifice) 69 a, which is an opening at thedistal end of tube 60. It is noted, that although not illustrated, anyone of the holes/nozzles described herein may include any type of valveor the like.

According to some embodiments, as presented in FIG. 6B, inflow 133 exitsvia a hole (nozzle/orifice) 69 b, which has a reduced diameter inrespect to the diameter of tube 60. Such a reduced diameter may providecryogenic fluid sprayed at defined pressure onto the treated regionand/or may enable a more efficient and accurate Joule Thompson effect.

According to some embodiments of the present invention,hole/nozzle/orifice/69 a or 69 b, as illustrated in FIGS. 6A and 6B, arealigned in the direction of tube 60 in order to result with frontalspray of inflow 133. According to other embodiments of the presentinvention, the hole/nozzle/orifice is directed in any appropriatedirection, including on the side of tube 60. According to someembodiments, the direction of the spray exiting any one of the nozzlesmay be changed by an element in the nozzle that may be directed in anyappropriate direction, wherein the direction of the element may bechanged automatically, manually, by electronic means, in response todata received from any appropriate sensors, and the like.

According to some embodiments, as illustrated in FIG. 6C, any number ofholes in tube 60 may exist, allowing inflow 133 to exit through a numberof holes 69 c. Further, holes 69 c, may be arranged in any desiredconfiguration and further, may each include a valve that may be closedor opened or partially opened, as required.

According to some embodiments, the nozzle is part of tube 60, accordingto other embodiments, as presented, e.g., in FIG. 6D, nozzle 69 d is anadditional component that is attached or connected to tube 60 by anyappropriate means. This connection or attachment may result fromfabrication advantages or constraints. According to some embodiments,any one of the nozzles may have a dedicated shape or size, for example,as illustrated in FIG. 6E, tapered nozzle 69 e may be utilized. The sizeand shape of the nozzles, as well as the number of nozzles may beoptimized according to each treatment, e.g., the size or type of thetreated region/lesion, the size of the body lumen in which the treatedregion/lesion is found, the size and shape of an inflated cryo-balloonand the like. In order to achieve dedicated shape for nozzle 69 e,additional process may be needed, such as thermal treatment ormachining, The inner diameter of any one of the inflow or injectionnozzles may be in the range of about 0.05-0.3 mm, while the innerdiameter of any one of the evacuation or outflow nozzles may be in therange of about 0.5-4 mm in average. It is noted that the cross-sectionof the nozzle may be of any appropriate shape, including circular,non-circular, oval, slit-shaped, or the like

Reference is now made to FIGS. 7A and 7B, which illustrate schematictransverse cross-sectional views of a cryotherapy device's distal endwithin an endoscope that has in-flow and out-flow channels, inaccordance with some embodiments of the present invention. According tosome embodiments, the cryotherapy device's distal end 24 directs theinflow 133 of coolant jet to the treated targeted region. Thecryotherapy catheter is inserted from the proximal end of the endoscopethrough its in-flow channel.

According to some embodiments of the current invention, and as detailedin FIGS. 1 to 6, evacuation of the expanded coolant, as well as anyother fluids present in the treated organ, is performed though acatheter/tube inserted into the organ via the endoscope. According tosome embodiments, the evacuation may be performed through one or severalinherent tubes or paths that may be part of the endoscope or that may beadded thereto or fed therethrough. For example, some endoscopes have anopening at their hack side (e.g. cystoscopic and hysteroscopicresectoscopes) where the cryotherapy device may be inserted. In suchendoscopes at least part of the evacuation can take place through thisback side (773) while some evacuation can be done through the out-flowexit (771) and/or through the in-flow entrance (772). It is furthernoted that the inflow, outflow and lumen pressure, affected by theinflow/outflow, may be controlled using such opening.

According to some embodiments of the present invention, the opening tothe evacuation tubes/catheters may be in close proximity to or at thesame or similar plane to inflow 133 (see, e.g., opening 77 a asillustrated in FIG. 7A). According to other embodiments severalcircumferential side evacuation openings 77 b, as illustrated in FIG.7B, are provided. As detailed herein, the position, number, size,diameter, etc. of the evacuation tubes may be altered and may be definedas required. Further, any one of the openings may be fitted with a valveallowing the opening to be opened, closed or partially closed, such thatany one of the openings may be used as required. The operation of thevalves may be electronic, manual, automatic, according to signalreceived from any appropriate sensors and the like.

Reference is now made to FIGS. 8A and 8B, which illustrate schematiclengthwise sectional views of cryotherapy devices fed into the treatedlumen through an endoscope, during ablation procedure in accordance withsome embodiments of the present invention. The dedicated ablatingcomponent, 83 a as illustrated in FIG. 8A or 83 b as illustrated in FIG.8B, may be an unfolded cryo balloon (as partially illustrated in FIG.4E).

In order to treat targeted region 82 an ablating device 80 is insertedinto endoscope 16 through its working channel in a way that device'sdistal end 24 exits the endoscope's distal end inside the body lumen 81,while device's proximal end 85 remains outside of the endoscope'sproximal end and outside of the treated patient, as illustrated in FIG.8A. According to some embodiments of the present invention, dedicatedablating component 83 a is unfolded within body lumen 81 in order totreat targeted region 82, as illustrated in FIG. 8A.

According to other embodiments of the current invention, a broaderablating component 83 b is unfolded within the body lumen 81 in order totreat targeted regions 82 and 82 b and maybe more regions at the sametime. Possibly the entire lumen may be treated if necessary.

Reference is now made to FIGS. 8C and 8D, which illustrate schematiclengthwise sectional views of a cryotherapy inflated device introducedvia an endoscope within the treated lumen during an ablation procedurein accordance with some embodiments of the present invention. Theinflated component may include several regions, each of which may have adifferent compliance. The inflated component may be constructed fromnon-compliant or semi-compliant part (0-8%), see element 83 c asillustrated in FIGS. 8C and 8D, and semi-compliant or compliant part(5-200%), see element 83 d as illustrated in FIGS. 8C and 8D. Accordingto some embodiments, element 83 c may be prepared from any appropriatetype of metal or plastic. According to some embodiments, element 83 cmay have a folded and unfolded configuration.

According to some embodiments, the cold energy is transferred to thetissue via compliant/semi-compliant element 83 d. As shown in thefigures, according to some embodiments, only a certain part of thecryo-balloon may come in contact with the treated area, while otherregions in the treated lumen are not in direct contact with thecryo-balloon. Element 83 d may be an inflatable component, whereinelement 83 c may be a structured element designed to hold and/orpartially define the shape of element 83 d. The inflated component 83 dmay be kept unfolded while within endoscope 16 (FIG. 8C) and its shapeis such that when inflated (by inflow 133 or other means), element 83 dis directed toward the targeted area, transferring cold energy thereto.

Reference is now made to FIGS. 8E to 8G, which illustrate schematiclengthwise sectional views of a cryotherapy inflated device introducedinside lumen during an ablation procedure in accordance with someembodiments of the present invention. FIG. 8E illustrates the inflatedcomponent inside the lumen close to the treated area 82 c, having anactive part 83 d. FIG. 8F illustrates inflated component with lowcompliance (0-8%) active region 83 d 1, while FIG. 8G illustratesinflated component with high or semi compliance (5-200%) active region83 d 2. As illustrated in the figures, use of a high or semi complianceinflated element may result with optimal fitting of the device to thetreated area, since the contact of the device with the treated area isoptimal.

Reference is now made to FIGS. 9A and 9B, which illustrate schematiclengthwise sectional views of an ablation device's distal end 93 inaccordance with some embodiments of the present invention. According tosome embodiments, unfolded distal end 934 a, which is illustrated inFIG. 9A, may comprise supporting ribs as well as a cryo-ballooncomponents. According to some embodiments of the current invention,unfolded distal end 934 a is inserted into the body lumen through sheath99 (which may be the endoscope's working channel itself) by pushingcatheter or wire 931. While the ablating distal end 934 a is positionedwithin the body lumen in the proximity of the targeted region (see FIGS.8A and 8B), user may manipulate bar (or lever, valve, faucet orcontroller) 933, in order to unfold the ablating distal end 934 b asillustrated in FIG. 9B, and then activate the ablating mechanism (RFand/or Cryo).

Some embodiments of the invention are directed to RFA devices andablation methods, wherein a folded RF mesh may be introduced via anendoscope to be unfolded within a body lumen to treat a targeted area.For example, the cryo-balloon presented in FIGS. 8A-D and 9A-B may bereplaced by an RF mesh.

The preceding specific embodiments are illustrative of the practice ofthe techniques of this disclosure. It is to be understood, therefore,that other expedients known to those skilled in the art or disclosedherein may be employed without departing from the scope of the followingclaims.

It is the intent of the Applicant(s) that all publications, patents andpatent applications referred to in this specification are to beincorporated in their entirety by reference into the specification, asif each individual publication, patent or patent application wasspecifically and individually noted when referenced that it is to beincorporated herein by reference. In addition, citation oridentification of any reference in this application shall not beconstrued as an admission that such reference is available as prior artto the present invention. To the extent that section headings are used,they should not be construed as necessarily limiting. In addition, anypriority document(s) of this application is/are hereby incorporatedherein by reference in its/their entirety.

What is claimed is:
 1. A method of treating tissue within an organhaving a lumen, said method comprising: introducing a cryotherapy deviceinto a lumen of an organ via an endoscope; injecting expandablecryo-fluid through at least one inflow channel of the cryotherapydevice, directly or indirectly, into the organ lumen, such that theexpandable cryo-fluid exits from said inflow channel and expands,directly or indirectly, in the organ lumen thereby freezing at leastpart of the treated tissue; detecting an indication with regard to atleast one parameter of said organ lumen, and/or at least one parameterof at least one outflow channel of the cryotherapy device, and/or atleast one parameter of said at least one inflow channel and evacuatingsaid expanded cryo-fluid, directly or indirectly, through said at leastone outflow channel of the cryotherapy device according to said detectedindication, from the organ lumen.
 2. The method according to claim 1,wherein said at least one parameter of said organ lumen comprisespressure accumulation in said organ lumen, and wherein said evacuatingcomprises evacuating said expanded cryo-fluid according to said detectedindication of said pressure accumulation.
 3. The method according toclaim 1, wherein said at least one parameter of said at least oneoutflow channel and/or said at least one inflow channel comprises flowspeed, flow direction, temperature and/or pressure.
 4. The methodaccording to claim 1, wherein said injecting comprises providing saidexpandable cryo-fluid to at least one element at a distal end of thedevice, wherein said at least one element defines a channel between saidinflow channel and said organ lumen and selectively directs saidexpandable cryo-fluid from the distal end of the device to at least onetargeted area within the organ lumen, such that the expandablecryo-fluid exits from said inflow channel through said at least oneelement and expands, directly or indirectly, in the organ lumen therebyfreezing at least part of the treated tissue.
 5. The method according toclaim 2, comprising controlling said injecting and/or said evacuating bya controller receiving data from at least one sensor that gathers dataregarding pressure in said organ lumen.
 6. The method according to claim5, wherein said controlling comprises controlling said injecting and/orsaid evacuating to maintain pressure levels in said organ lumen between10 mBar and 100 mBar.
 7. The method according to claim 1, comprisingcontrolling said injecting and/or said evacuating by a controllerreceiving data from at least one sensor that gathers data with regard toat least one of, pressure in said treated organ lumen, a temperature ofthe treated organ lumen, flow rate, and flow time, or any combinationthereof.
 8. The method according to claim 1, wherein said detectingcomprises detecting an indication with regard to temperature within saidorgan lumen; and wherein said method comprising stopping said injectingif a temperature within said organ lumen is below 10 degrees Celsius. 9.The method according to claim 1, wherein said detecting comprisesdetecting blockage of said at least one outflow channel, and whereinsaid method comprising controlling said injecting according to thedetected blockage.
 10. The method according to claim 1, wherein saidorgan comprises the bladder, and wherein said introducing comprisesintroducing said device into the bladder, via a urethra.
 11. The methodaccording to claim 1, wherein said evacuating comprises evacuating bodyfluids from the bladder through at least one outflow channel.
 12. Themethod according to claim 1, wherein the cryo-fluid is selected fromliquid nitrogen, carbon dioxide (CO2), nitrous oxide (N2O), or anycombination thereof.
 13. The method according to claim 1, wherein saidintroducing comprises bending said cryotherapy device within said organin sharp angular movements larger than 90 degrees.
 14. The methodaccording to claim 1, wherein said organ lumen comprises a cervix, aprostate, a urethra, a ureter or a uterus.
 15. The method according toclaim 1, wherein at least one inflow channel and at least one outflowchannel are the same channel, wherein the direction of flow therethroughis controlled by a controller.
 16. The method according to claim 1,wherein said injecting comprises injecting said expandable cryo-fluidthrough at least one frontal inflow opening of the cryotherapy deviceinto said organ lumen, and wherein said evacuating comprises evacuatingsaid expanded cryofluid through at least one frontal outflow opening ofthe inflow channel.
 17. The method according to claim 1, wherein saidevacuating comprises evacuating said expanded cryofluid through at leastone side outflow opening of the outflow channel.
 18. The methodaccording to claim 1, wherein said injecting comprises injecting saidexpandable cryo-fluid through a plurality of side inflow openings ofsaid inflow channel, into said organ lumen.
 19. The method according toclaim 1, wherein said method is a method for treating bladder cancer,comprising diagnosing a patient with bladder cancer, wherein saidintroducing comprises introducing said cryotherapy device into a bladderof said patient, and wherein said injecting comprises directing saidexpandable cryo-fluid at a cancerous tumor in said bladder, therebyfreezing at least part of said cancerous tumor.
 20. The method accordingto claim 1, wherein said method is a method for treating cervix cancer,wherein said introducing comprises introducing said cryotherapy deviceinto a cervix of a patient diagnosed with cervix cancer, and whereinsaid injecting comprises directing said expandable cryo-fluid at acancerous tumor in said cervix, thereby freezing at least part of saidcancerous tumor.
 21. The method according to claim 1, wherein saidmethod is a method for treating prostate cancer, wherein saidintroducing comprises introducing said cryotherapy device into aprostate of a patient diagnosed with prostate cancer, and wherein saidinjecting comprises directing said expandable cryo-fluid at a canceroustumor in said prostate, thereby freezing at least part of said canceroustumor.
 22. The method according to claim I, wherein said method is amethod for treating urethral cancer, wherein said introducing comprisesintroducing said cryotherapy device into a urethra of a patientdiagnosed with urethral cancer, and wherein said injecting comprisesdirecting said expandable cryo-fluid at a cancerous tumor in saidurethra, thereby freezing at least part of said cancerous tumor.
 23. Themethod according to claim wherein said method is a method for treatingureteral cancer, wherein said introducing comprises introducing saidcryotherapy device into a ureter of a patient diagnosed with ureteralcancer, and wherein said injecting comprises directing said expandablecryo-fluid at a cancerous tumor in said ureter, thereby freezing atleast part of said cancerous tumor.
 24. The method according to claim 1,wherein said method is a method for treating uterus cancer, wherein saidintroducing comprises introducing said cryotherapy device into a uterusof a patient diagnosed with uterus cancer, and wherein said injectingcomprises directing said expandable cryo-fluid at a cancerous tumor insaid uterus, thereby freezing at least part of said cancerous tumor. 25.The method according to claim 1, wherein said method is a method fortreating upper tract urothelial cancer, wherein said introducingcomprises introducing said cryotherapy device into a ureter or kidney ofa patient diagnosed with upper tract urothelial cancer, and wherein saidinjecting comprises directing said expandable cryo-fluid at a canceroustumor in said ureter or kidney, thereby freezing at least part of saidcancerous tumor.